This study will determine the feasibility of using autologous activated T cells for the treatment of B-CLL. Xcyte s technology uses para-magnetic beads covalently coated with anti-CD3 and anti-CD28 anti-bodies, which makes the bead a potent polyclonal activator of T cells. Cells generated this way have been used at the University of Chicago to treat relapsed/chemorefractory B Cell-NHL patients. This trial represents the first successful use of an ex-vivo costimulatory autologous T cell immunotherapeutic approach for patients with this malignancy. B-CLL patients present special difficulties for this therapy, including high leukemic burden in the blood, associated with T cell immunosuppression and hypo- gammaglobulinemia. The proposed study is designed to address using Xcyte s technology in a clinical trial for B-CLL patients who have failed primary therapy. The study will assess the ability of coordinated CD3xCD28 activation to expand T cells from the peripheral blood of B-CLL patients to therapeutically relevant numbers, and to correct T cell defects which prevent them from responding to autologous leukemia cells. Successful demonstration of these aims will justify the initiation of a phase I clinical trial in B-CLL conducted jointly by Xcyte Therapies and collaborators at the Oregon Health Sciences University. PROPOSED COMMERCIAL APPLICATION Xcyte Therapies has built a GMP manufacturing facility to generate activated T cells for clinical trials. A pivotal trial for 3x28 activated T cells will begin in 2000. About 20,000 NHL patients will be eligible for this therapy in the USA, and another 20,000 patients with other malignancies, such as B-CLL will also be eligible. The therapy may have applications to breast, lung and prostate cancer as well.